Evidence of simian immunodeficiency virus (SIV) infection has been reported for 27 different species of African non-human primates. Two of these viruses, SIVcpz from chimpanzees and SIVsm from sooty mangabeys, are the cause of AIDS in humans. Together, they have been transmitted to humans on at least eight occasions. An important scientific and public health concern thus is whether and to what extent humans are exposed to additional SIV strains (besides SIVsm and SIVcpz), and whether such exposure has led to zoonotic transmission. An additional, more fundamental question pertains to the spectrum of SIV diversity that exists in wild-living African primates and the ecological niche occupied by this broad family of primate lentiviruses. In this grant application, we propose to address these questions in Cameroon, a country known to lie within the center of HIV-1 groups M, N, and O endemicity and to harbor a diverse set of SIV- infected non-human primates. We have assembled a research team of co-investigators, with each member of the team bringing essential expertise, unique capability, and work scope to the project. On the basis of published work and research in progress, we demonstrate that our goals are scientifically and technically feasible and that our team is uniquely positioned to accomplish them. Specific aims of the project are: 1. To determine the full spectrum of SIV infected non-human primates in Cameroon. We will use serologic and PCR-based approaches to test primate bushmeat confiscated by the Ministry of Forest and Environment as well as fecal and urine samples collected from wild apes for SIV specific antibody and nucleic acids. 2. To determine the genetic and phylogenetic identity of all SIV lineages infecting primate species in Cameroon. We will PCR amplify, clone and sequence full-length genomes for all major SIV lineages, and construct replication competent proviral clones for basic biological and immunological studies. 3. To determine the prevalence of SIV infection in wild-living primates in Cameroon. We will develop sensitive, lineage specific serological and PCR based assays and apply them to determine the prevalence of SIV in each naturally infected primate species. 4. To assess the prevalence of SIV infection in human populations from Cameroon and surrounding areas of west central Africa. We will use novel screening and confirmatory assays to analyze existing serum banks from west equatorial human populations for evidence of SIV infection. We expect these studies to yield a complete record of all naturally infected primate species in Cameroon, an accurate assessment of their levels of infection, and a first approximation of human zoonotic risk.